The Narcotic Drug and Opioid Peptide Basic Research Project enters its 31st year with continued vigor and enthusiasm. Several aspects of the Center are logical extensions of efforts of earlier years; other aspects represent entirely new areas of interest. Included in the former category are studies that refine and analyze the pharmacological effects of opioids in the rhesus monkey. Our research on the analgesic, respiratory, and reinforcing effects of opioids will continue into new avenues. In addition, studies using newly developed analgesia are included that may provide evidence for novel, additional pathways through which opioids can provide therapeutic action against pain and inflammatory processes. Similarly, studies of the reinforcing effects of opioids will be extended to new procedures that may provide evidence of increasing reinforcing effects of opioids during withdrawal and eventually, protracted withdrawal. The drug discovery program will continue to evaluate the in vivo and in vitro effects of opioids in rodents and in vivo effects of opioids in nonhuman primates. One objective of this aspect of the Center is to determine the mechanism by which buprenorphine exerts its novel actions that make it an extremely interesting pharmacotherapy for opioid abuse. The work of the human behavioral pharmacology laboratory continues on the focus of the evaluation of buprenorphine as a pharmacotherapy and makes direct comparison to methadone in some its pharmacology. Studies utilizing labeled carfentanil in PET imaging studies will compare buprenorphine's binding to central mu-receptors with its antagonism of hydromorphone's pharmacological effects. A new area of research is a major chemical venture toward the development of radiolabeled PET ligands specific to opioid function in pharmacologicical, physiological, and pathophysiological Conditions in primates and humans.